Description
U-0126 is a selective, non-ATP competitive inhibitor of mitogen activated protein kinase kinase (MEK), inhibiting MEK1 and MEK2 with IC₅₀ values of 72 nM and 58 nM, respectively (Favata et al.; Scherle et al.). It shows little or no inhibition at micromolar levels of other kinases such as ERK, protein kinase C (PKC), c-Jun N-terminal kinases (JNK), other MAP kinase kinases (MKK3, MKK4, MKK6), cyclin-dependent kinases (CDK2, CDK4), ABL, and RAF (Favata et al. 1998). U-0126 also antagonizes AP-1 transcription and selectively inhibits promoters containing AP-1 response elements (Favata et al.).
MAINTENANCE & SELF-RENEWAL
· In combination with basic FGF, Activin A, and a PKC inhibitor, U-0126 promotes maintenance of human pluripotent stem cells (Kinehara et al.)
· Used alone with MEF-conditioned medium, U-0126 inhibits self-renewal of human pluripotent stem cells, leading to differentiation, without affecting proliferation or survival (Li et al.).
· Inhibits glutamate-induced oxidative stress in mouse hippocampal HT22 cells and rat primary cortical cultures (Satoh et al.; Ong et al.).
· Neuroprotective in a gerbil ischemia model and in primary mouse neurons cultured under hypoxia (Namura et al.).
IMMUNOLOGY
· Inhibits T-cell proliferation against certain antigenic stimuli by reducing IL-2 mRNA levels (DeSilva et al.).
DISEASE MODELING
· Activates peroxisome proliferator activated receptor (PPAR) co-activator 1α (PGC-1α) and prevents neurotoxicity and spatial memory impairment in rats challenged by amyloid beta (Aβ; Ashabi et al.).
